Author/Authors :
Atsushi Akao، نويسنده , , Shouichi Hiraga، نويسنده , , Takehiko Iida، نويسنده , , Asayuki Kamatani، نويسنده , , Masashi Kawasaki، نويسنده , , Toshiaki Mase، نويسنده , , Takayuki Nemoto، نويسنده , , Nobuya Satake، نويسنده , , Steven A Weissman، نويسنده , , David M Tschaen، نويسنده , , Kai Rossen، نويسنده , , Daniel Petrillo، نويسنده , , Robert A. Reamer، نويسنده , , R.P Volante، نويسنده ,
Abstract :
DNA topoisomerase I inhibitors are currently under investigation as cancer chemotherapy agents of which indolocarbazole glycoside (1) has been identified as a promising candidate. A practical, scalable synthesis of 1 that limits the isolation of cytotoxic compounds to only that of the final product is described. The convergent process features a novel phase transfer-promoted glycosylation of aglycone core (4); subsequent hydrolysis provides anhydride (8). The hydrazine fragment (3), which is coupled with 8, is synthesized via a modification of existing procedures. The coupled product (2) is subsequently hydrogenated to provide 1 in excellent purity via direct crystallization (>99.3 A%).
